The phenotypic consequences of the premature fusion of cranial sutures, craniosynostosis, range from subtle to conspicuous and the etiology and pathogenesis of this condition is heterogeneous. A genetic basis has been determined for some syndromes that involve craniosynostosis as well as for a family affected with Boston type craniosynostosis. If craniosynostosis results from changes in genes regulating development, then an understanding of postnatal craniofacial development in craniosynostosis can provide information about the pathogenesis of this condition, and potentially about the generation of morphology at the molecular level. This project focuses on the postnatal developmental aspects of isolated craniosynostosis, specifically on the three dimensional (3D) growth pattern of the skull. We will systematically archive high resolution computed tomography (CT) scans of patients seen in the Greater Baltimore area. Two types of isolated craniosynostosis will be targeted initially; coronal and sagittal craniosynostosis. These groups are chosen because they are relatively large (we anticipate 20 coronal and 17 sagittal cases/year) and it is unlikely that these groups include any functional synostoses. Since each craniosynostosis patient underscores a minimum of three CT studies, these clinically indicated scans will eventually comprise a longitudinal data base. A normative sample will be formed using CT scans of patients unaffected by craniosynostosis. Previous work has demonstrated that classes of craniosynostosis can be differentiated by analysis of growth patterns. Using morphometric methods developed by Richsmeier and co-workers, three dimensional growth trajectories of the skull will be calculated for all case of isolated sagittal and isolated coronal synostosis. Within each of these diagnostic categories, a clustering analysis will be done in order to group individual cases on the basis of similarity in growth pattern. We propose that differences in growth pattern among patients with similar morphological findings reflect fundamental etiological and pathophysiologic differences. Details of the 3D growth patterns for individuals within these clusters can be compared to identify aspects of the growth pattern unique to a cluster. The clusters we define will be evaluated against the growth patterns calculated from the normative data and in terms of genetic and epidemiological information gathered from other projects within the Center for Craniofacial Development and Disorders in order to further define the basis for heterogeneity in craniosynostosis.